Nimacimab Advanced Drug Monograph

Nimacimab Report

Name: Nimacimab Name (English): Nimacimab DrugBank ID: DB15115 Type: Biotech (Humanized monoclonal antibody) CAS Number: 2098636-09-8

Mechanism of Action: Nimacimab is a first-in-class humanized monoclonal antibody that acts as a negative allosteric modulator to inhibit CB1 signaling in the periphery. It binds to the CB1 receptor, a G-protein coupled receptor, and prevents its activation by endogenous cannabinoids. This peripheral inhibition of CB1 has shown potential in promoting energy expenditure, fat breakdown, improving leptin sensitivity, and modulating hunger and satiety. Unlike earlier CB1 inhibitors, nimacimab exhibits limited penetration into the central nervous system, potentially avoiding the neuropsychiatric side effects associated with central CB1 blockade.

Clinical Trials: Nimacimab is currently in Phase 2 clinical development for obesity.

• Phase 2a (CBeyond™): A randomized, double-blind, placebo-controlled study (NCT06577090) evaluating the efficacy and safety of nimacimab as a monotherapy and in combination with semaglutide (Wegovy®) in overweight or obese adults. The trial is fully enrolled, with interim data expected in late Q3/early Q4 2025. An open-label extension to 52 weeks has been approved.
• A Phase 2 study was also planned for diabetic gastroparesis, but no recent development has been reported, suggesting it may be discontinued.
• A previous Phase 1b study in patients with non-alcoholic fatty liver disease (NAFLD) and diabetes or prediabetes showed no serious adverse events and positive trends in some metabolic biomarkers.

Preclinical Studies:

• In a diet-induced obesity (DIO) mouse model, nimacimab demonstrated significant dose-dependent weight loss, fat mass reduction, lean mass preservation, and improved glucose tolerance.
• Combination therapy of nimacimab with tirzepatide in a DIO model resulted in over 30% weight loss, showing an additive effect compared to either drug alone.
• In vitro studies suggest nimacimab has superior potency in inhibiting CB1 compared to small molecule inhibitors like monlunabant, especially under pathological conditions with elevated CB1 agonist concentrations.

Side Effects: Data from the Phase 1b study in NAFLD patients indicated that the most frequently reported adverse events in both nimacimab and placebo groups were diarrhea, headache, dizziness, upper respiratory tract infection, and nausea/vomiting. Notably, no significant neuropsychiatric adverse events were observed in preclinical or Phase 1 studies.

Regulatory Status: Nimacimab is currently an investigational drug. The Investigational New Drug (IND) application for nimacimab in obesity and chronic kidney disease was cleared by the U.S. Food and Drug Administration (FDA).

Developer: Skye Bioscience, Inc. (formerly Bird Rock Bio).